Creutzfeldt-Jakob Disease Health Article

Definition

Creutzfeldt-Jakob disease (CJD) is a transmissible, rapidly progressing, fatal neurodegenerative disorder related to "mad cow disease."

Description

Before 1995, Creutzfeldt-Jakob disease was little known outside the medical profession. Indeed, most physicians did not know much about the disease, and few had ever seen a patient with the disease. But with the discovery of a "new variant" form, the possibility that those with the disease became infected simply by eating beef, and the radical theory that the infectious agent is a rogue protein, CJD has become one of the most talked about diseases in the world, and has taken on a significance far beyond the small number of deaths it currently causes each year.

First described in the 1920s, CJD is a neurodegenerative disease causing a rapidly progressing dementia which ends in death, usually within eight months of the onset of symptoms. It is also a very rare disease, affecting only about one in every million people in the population worldwide. In the United States, CJD is thought to affect about 250 people each year. CJD affects adults of all ages, but is rare in young adults and most common between ages 50 and 75.

Spongiform encephalopathies

The most obvious pathologic feature of CJD is the formation of numerous, fluid-filled spaces in the brain (vacuoles), giving the brain a sponge-like appearance. CJD is one of several human spongiform encephalopathies, diseases that produce this characteristic change in brain tissue. Others include kuru; Gerstmann-Straussler-Scheinker dis- ease, predominantly characterized by cerebellar ataxia; and fatal familial insomnia, associated with progressive insomnia, autonomic system dysfunction, and weakness caused by motor system dysfunction.

Kuru was prevalent among the Fore people in Papua New Guinea,. The disease was spread from infected individuals after their deaths through the practice of ritual cannibalism, in which the relatives of the dead person honored him by consuming his organs, including the brain. Discovery of the infectious nature of kuru won the Nobel Prize for Carleton Gadjusek in 1976 and also alerted the medical world to the possibility of slow-acting infectious agents, collectively termed slow-virus diseases. The incubation period for kuru was four to 30 years or more. While kuru has virtually disappeared following the cessation of cannibalistic practices, several new cases continue to arise each year.

Cases of CJD have been grouped into three types: familial, iatrogenic, and sporadic.

• Familial CJD, representing 5–15% of cases, is inherited in an autosomal dominant manner, meaning that either parent may pass along the disease to a child, who may then develop CJD later in life.
• Iatrogenic CJD occurs when a person is infected during a medical procedure, such as organ donation and transplantation, blood transfusion, or brain surgery. The rise in organ donation has increased this route of transmission. Grafts of infected corneas and dura mater (the tissue covering the brain) have been linked with the transmission of CJD. Another source is hormones concentrated from the pituitary glands of cadavers, some of whom carried CJD, for use in people with growth hormone deficiencies. Iatrogenic infection represents a small fraction of all cases. The incubation period between exposure to the infectious agent is very long and is estimated to be from less than 10 to more than 30 years.
• Sporadic CJD represents at least 85% of all cases. Sporadic cases have no identifiable source of infection. Death usually follows the appearance of the first symptoms within eight months.

Animal forms and "mad cow disease"

Six different forms of spongiform encephalopathy are known to occur in other mammals: scrapie in sheep, recognized for more than 200 years; chronic wasting dis- ease in elk and mule deer in Wyoming and Colorado; transmissible mink encephalopathy; exotic ungulate encephalopathy in some types of zoo animals; feline spongiform encephalopathy in domestic cats; and bovine spongiform encephalopathy (BSE) in cows. All of these are classified as slow-virus diseases.

BSE was first recognized in Britain in 1986. Besides the spongiform changes in the brain, BSE causes dementia-like behavioral changes. This is the origin of the name "mad cow disease." BSE is thought to be an altered form of scrapie that was transmitted to cows when sheep offal (slaughterhouse waste) was included in their feed.

The use of slaughterhouse offal in animal feed has been common in many countries and has been practiced for at least 50 years. The trigger for the BSE epidemic in Britain seems to have come in the early 1980s, when the use of organic solvents for preparation of offal was halted there. It seems likely that these solvents had destroyed the scrapie agent, thereby preventing infection. The change in preparation procedure opened the way for the agent to "jump species" and cause BSE in cows that consumed scrapie-infected meal. The slaughter of infected (but not yet visibly sick) cows at the end of their useful farm lives, and the use of their carcasses for feed, spread the infection rapidly and widely. For at least the first year after BSE was initially recognized in British herds, infected bovine remains continued to be incorporated into feed, spreading the disease still further. It is thought that most cows with BSE became infected as a result of eating meal containing offal from other cows, not sheep. Although milk from infected cows has never been shown to contain or pass the infectious agent, passage from infected mother to calf has occurred through unknown means.

Beginning in 1988, the British government took steps to stop the spread of BSE, banned the use of bovine offal in feed and other products, and ordered the slaughter of infected cows. By then, the slow-acting agent had become epidemic in British herds. In 1992, it was diagnosed in over 25,000 animals (1% of the British herd). By mid-1997, the cumulative number of BSE cases in the United Kingdom had risen to more than 170,000. The feeding ban apparently did slow the spread of the epidemic. The number of new cases each week fell from a peak of 1,000 in 1993 to fewer than 300 two years later.

The export of British feed and beef to member countries was banned by the European Union, but cases of BSE had developed in Europe by then. About 1,000 cases were identified in Europe by 1997. In 1989, the United States banned the import of British beef and began monitoring U.S. herds in 1990. As of 2001, the U.S. Department of Agriculture reports that BSE has not been detected in the United States. One case has been reported in Canada in a cow imported from Britain.